Traumatic Brain Injury (TBI)NCT04796207
The Effects of Fish Oil Supplementation on the Brain Health of Collegiate Football Athletes
A study testing Fish Oil (DPA+EPA 2:1 ratio) Capsules and High Oleic Safflower Oil Capsules in people with Traumatic Brain Injury (TBI) and Chronic Traumatic Encephalopathy (CTE), run by University of Arizona at 1 site in United States.
Trial summary
Determine if the daily docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) supplement will reduce serum levels of biomarkers of sub-concussion injuries over a course of American football season among collegiate football athletes. Read more about this study
- Who is it for?
- Ages 18 to 25 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Traumatic Brain Injury (TBI), Chronic Traumatic Encephalopathy (CTE)
- What is being tested?
- Fish Oil (DPA+EPA 2:1 ratio) Capsules and High Oleic Safflower Oil Capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 28 May 2019to 28 Jan 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 25 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 1) University of Arizona National Collegiate Athletic Association (NCAA) Division I American football athletes cleared to participate in university athletics as determined by the team physician.
Who cannot join
- Chronic daily anti-inflammatory drugs (>20 d).
- Medications for blood lipids.
- Active fish oil or omega-3 fatty acid supplementation.
- Consumption of more than two servings of fish per week.
- Injured and unable to participate in regularly schedule conditioning or competitions.
- Acute concussion experienced within 30 days of starting the study.
- Fish allergies.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Study of Effect of Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA) Supplementation on Biomarkers of Sub-Concussion Injuries in American Football
Determine if the daily docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) supplement will reduce serum levels of biomarkers of sub-concussion injuries over a course of American football season among collegiate football athletes.
Read the detailed description
American football is one of the most popular sports in the U.S. Yet this sport is associated with increased risk of concussion (also known as mild traumatic brain injury, or mTBI) and sub-concussive injury from repeated head impacts (RHI) due to the aggressive and high-speed nature of the game. Current protective equipment used by players are not sufficient to reduce concussion incidence and severity, nor are there any therapeutics available to prevent concussion. This study is a randomized, double-blind, placebo controlled trial to determine if an omega-3 polyunsaturated fatty acid (PUFA) fish oil supplement containing 3.0 grams of docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) can reduce blood biomarkers of sub-concussion injuries compared to placebo (high-oleic safflower oil) over a course of the American football season among collegiate football athletes.
The dosage of DHA/EPA used in this study is generally safe, and procedures involved, monthly blood draws, surveys, and Magnetic Resonance Imaging (MRI), pose minimal risks to participants. While this study provides no direct benefit to participants, successful outcomes of this study can benefit the society by shedding light on development of potential preventative therapeutics for sports-induced mTBI and brain injury from RHI. The risk-benefit profile is appropriate for conducting this study. Based on preclinical studies and previous clinical study results, the investigators expect that in comparison to placebo treatment, DHA and EPA treatment throughout the course of one American football season can maintain lower levels of sub-concussion associated biomarkers, inflammatory cytokines, and cardiovascular risk markers. The investigators also expect participants treated with DHA and EPA to have lower brain MRI imaging markers of sub concussion injury.
- Being tested
- Fish Oil (DPA+EPA 2:1 ratio) Capsules, High Oleic Safflower Oil Capsules
- Keywords
- CTE (Chronic Traumatic Encephalopathy), mTBI (Mild Traumatic Brain Injury), Concussion, MRI, Nf-L (Neurofilament Light Chain), Biomarker, Football
- Medical subject headings
- Brain Injuries, Traumatic, Chronic Traumatic Encephalopathy, Brain Concussion, Charcot-Marie-Tooth disease, Type 1F
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fish Oil (DPA+EPA 2:1 ratio) CapsulesDietary supplement
The Treatment Arm intervention consists of providing participants with 3 grams of DHA and EPA (2:1 weight ratio) in capsular form. In order to meet the required 3 grams of DHA and EPA, participants were given 6 capsules to be taken with meals (preferably breakfast, although capsules were provided at lunch when they couldn't be provided at breakfast). Capsules were given 5 times a week during the regular football season.
High Oleic Safflower Oil CapsulesDietary supplement
The Placebo Arm intervention consists of providing participants with 3 grams of high-oleic safflower oil in a 1:1 allocation ratio in capsular form. In order to maintain the "study masking", participants in the Placebo Arm were given 6 capsules (the same as the Treatment Arm) to be taken with meals (preferably breakfast, although capsules were provided at lunch when they couldn't be provided at breakfast). Capsules were given 5 times a week during the regular football season.
| Study group | Role | What they receive |
|---|---|---|
| Fish Oil Capsules | Experimental | Participants in the treatment arm will receive 3 grams of DHA and EPA (2:1 weight ratio) 5 times a week for 25-weeks during regular football season. Receives: Dietary Supplement: Fish Oil (DPA+EPA 2:1 ratio) Capsules |
| Safflower Oil Capsules | Placebo comparator | Participants in the treatment arm will receive 3 grams of high-oleic safflower oil (in a 1:1 allocation ratio) 5 times a week for 25-weeks during regular football season. Receives: Dietary Supplement: High Oleic Safflower Oil Capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Brain Biomarkers Due to Sub-concussion Injury - Nf-L
This primary outcome covers the change in the plasma brain biomarker Neurofilament Light Chains (Nf-L) due to sub-concussion injury from baseline to predetermined measurement time points. Nf-L (neuron specific intermediate proteins) are released upon injury to neurons and axons. Measured in picograms per milliliter (pg/ml)
Measured: Baseline, Week 17, Week 26
Changes in Sub-concussion Injury Related Inflammation Biomarkers - TNF-α
This primary outcome covers the change in the plasma inflammation biomarker Tumor Necrosis Factor-alpha (TNF-α), a cytokine and mediator of inflammation, due to sub-concussion injury from baseline to predetermined measurement time points. TNF-α is measured in picograms per milliliter (pg/ml).
Measured: Baseline ans Week 26
Changes in Sub-concussion Injury Related Inflammation Biomarkers - IL-6
This primary outcome covers the change in the plasma inflammation biomarker Interleukin-6 (IL-6), a cytokine and mediator of inflammation, due to sub-concussion injury from baseline to predetermined measurement time points. IL-6 is measured in picograms per milliliter (pg/ml)
Measured: Baseline; Week 17; Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2021
- Study start28 May 2019
- Primary completion28 Jan 2020
- Study completion28 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain Injury (TBI)Studies of the same condition, open and under way.
- More trials run by University of ArizonaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized to treatment (3 grams DHA and EPA (2:1 weight ratio)) or placebo (3 grams high-oleic safflower oil in a 1:1 allocation ratio) based on their position on the football team and roster depth (starter vs. non-starter). Participants will be recruited as a single cohort. After screening, participants will be treated with DHA and EPA or matching placebo for 25 weeks (a full course of an American football season, including summer camp training sessions). A follow-up visit is scheduled 7 weeks after the final dosing at week 32 for recovery and adverse event evaluation.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Floyd Chilton, University of Arizona
- Investigators
- Floyd Chilton, Ph.D., Principal investigator, University of ArizonaRoberta Brinton, Ph.D., Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04796207
- Sponsor's protocol ID
- IRB1904553365
- Status last verified
- Apr 2025
- First submitted
- 3 Mar 2021
- Last updated
- 9 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Raikes AC, Hernandez GD, Mullins VA, Wang Y, Lopez C, Killgore WDS, Chilton FH, Brinton RD. Effects of docosahexaenoic acid and eicosapentaoic acid supplementation on white matter integrity after repetitive sub-concussive head impacts during American football: Exploratory neuroimaging findings from a pilot RCT. Front Neurol. 2022 Sep 15;13:891531. doi: 10.3389/fneur.2022.891531. eCollection 2022.
PubMed 36188406
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Effect of Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA) Supplementation on Biomarkers of Sub-Concussion Injuries in American Football
- ClinicalTrials.gov ID
- NCT04796207
- Acronym / sponsor ID
- IRB1904553365
- Keywords
- CTE (Chronic Traumatic Encephalopathy), mTBI (Mild Traumatic Brain Injury), Concussion, MRI, Nf-L (Neurofilament Light Chain), Biomarker, Football
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Study start
- 28 May 2019 (actual)
- Primary completion
- 28 Jan 2020 (actual)
- Study completion
- 28 Jan 2020 (actual)
- First posted
- 12 Mar 2021 (actual)
- Results
- Posted 9 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Determine if the daily docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) supplement will reduce serum levels of biomarkers of sub-concussion injuries over a course of American football season among collegiate football athletes.
Detailed description
American football is one of the most popular sports in the U.S. Yet this sport is associated with increased risk of concussion (also known as mild traumatic brain injury, or mTBI) and sub-concussive injury from repeated head impacts (RHI) due to the aggressive and high-speed nature of the game. Current protective equipment used by players are not sufficient to reduce concussion incidence and severity, nor are there any therapeutics available to prevent concussion. This study is a randomized, double-blind, placebo controlled trial to determine if an omega-3 polyunsaturated fatty acid (PUFA) fish oil supplement containing 3.0 grams of docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) can reduce blood biomarkers of sub-concussion injuries compared to placebo (high-oleic safflower oil) over a course of the American football season among collegiate football athletes.
The dosage of DHA/EPA used in this study is generally safe, and procedures involved, monthly blood draws, surveys, and Magnetic Resonance Imaging (MRI), pose minimal risks to participants. While this study provides no direct benefit to participants, successful outcomes of this study can benefit the society by shedding light on development of potential preventative therapeutics for sports-induced mTBI and brain injury from RHI. The risk-benefit profile is appropriate for conducting this study. Based on preclinical studies and previous clinical study results, the investigators expect that in comparison to placebo treatment, DHA and EPA treatment throughout the course of one American football season can maintain lower levels of sub-concussion associated biomarkers, inflammatory cytokines, and cardiovascular risk markers. The investigators also expect participants treated with DHA and EPA to have lower brain MRI imaging markers of sub concussion injury.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomized to treatment (3 grams DHA and EPA (2:1 weight ratio)) or placebo (3 grams high-oleic safflower oil in a 1:1 allocation ratio) based on their position on the football team and roster depth (starter vs. non-starter). Participants will be recruited as a single cohort. After screening, participants will be treated with DHA and EPA or matching placebo for 25 weeks (a full course of an American football season, including summer camp training sessions). A follow-up visit is scheduled 7 weeks after the final dosing at week 32 for recovery and adverse event evaluation.
| Arm | Type | Receives |
|---|---|---|
| Fish Oil Capsules | Experimental | Dietary Supplement: Fish Oil (DPA+EPA 2:1 ratio) CapsulesParticipants in the treatment arm will receive 3 grams of DHA and EPA (2:1 weight ratio) 5 times a week for 25-weeks during regular football season. |
| Safflower Oil Capsules | Placebo comparator | Dietary Supplement: High Oleic Safflower Oil CapsulesParticipants in the treatment arm will receive 3 grams of high-oleic safflower oil (in a 1:1 allocation ratio) 5 times a week for 25-weeks during regular football season. |
Who may qualify
- Ages
- 18 to 25 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- 1) University of Arizona National Collegiate Athletic Association (NCAA) Division I American football athletes cleared to participate in university athletics as determined by the team physician.
Key exclusion criteria (7 listed)
- Chronic daily anti-inflammatory drugs (>20 d).
- Medications for blood lipids.
- Active fish oil or omega-3 fatty acid supplementation.
- Consumption of more than two servings of fish per week.
- Injured and unable to participate in regularly schedule conditioning or competitions.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fish Oil (DPA+EPA 2:1 ratio) CapsulesThe Treatment Arm intervention consists of providing participants with 3 grams of DHA and EPA (2:1 weight ratio) in capsular form. In order to meet the required 3 grams of DHA and EPA, participants were given 6 capsules to be taken with meals (preferably breakfast, although capsules were provided at lunch when they couldn't be provided at breakfast). Capsules were given 5 times a week during the regular football season. | Dietary supplement | Fish Oil Capsules |
| High Oleic Safflower Oil CapsulesThe Placebo Arm intervention consists of providing participants with 3 grams of high-oleic safflower oil in a 1:1 allocation ratio in capsular form. In order to maintain the "study masking", participants in the Placebo Arm were given 6 capsules (the same as the Treatment Arm) to be taken with meals (preferably breakfast, although capsules were provided at lunch when they couldn't be provided at breakfast). Capsules were given 5 times a week during the regular football season. | Dietary supplement | Safflower Oil Capsules |
Primary outcome
Changes in Brain Biomarkers Due to Sub-concussion Injury - Nf-L
Time frame: Baseline, Week 17, Week 26
This primary outcome covers the change in the plasma brain biomarker Neurofilament Light Chains (Nf-L) due to sub-concussion injury from baseline to predetermined measurement time points. Nf-L (neuron specific intermediate proteins) are released upon injury to neurons and axons. Measured in picograms per milliliter (pg/ml)
Changes in Sub-concussion Injury Related Inflammation Biomarkers - TNF-α
Time frame: Baseline ans Week 26
This primary outcome covers the change in the plasma inflammation biomarker Tumor Necrosis Factor-alpha (TNF-α), a cytokine and mediator of inflammation, due to sub-concussion injury from baseline to predetermined measurement time points. TNF-α is measured in picograms per milliliter (pg/ml).
Changes in Sub-concussion Injury Related Inflammation Biomarkers - IL-6
Time frame: Baseline; Week 17; Week 26
This primary outcome covers the change in the plasma inflammation biomarker Interleukin-6 (IL-6), a cytokine and mediator of inflammation, due to sub-concussion injury from baseline to predetermined measurement time points. IL-6 is measured in picograms per milliliter (pg/ml)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36188406Raikes AC, Hernandez GD, Mullins VA, Wang Y, Lopez C, Killgore WDS, Chilton FH, Brinton RD. Effects of docosahexaenoic acid and eicosapentaoic acid supplementation on white matter integrity after repetitive sub-concussive head impacts during American football: Exploratory neuroimaging findings from a pilot RCT. Front Neurol. 2022 Sep 15;13:891531. doi: 10.3389/fneur.2022.891531. eCollection 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Floyd Chilton, Ph.D. principal investigator
University of Arizona
Roberta Brinton, Ph.D. principal investigator
University of Arizona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fish Oil (DPA+EPA 2:1 ratio) Capsules and High Oleic Safflower Oil Capsules in people with Traumatic Brain Injury (TBI) and Chronic Traumatic Encephalopathy (CTE), run by University of Arizona at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Brain Biomarkers Due to Sub-concussion Injury - Nf-L (time frame: Baseline, Week 17, Week 26). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04796207, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2025.